LYN LYN proto-oncogene, Src family tyrosine kinase
ENSG00000254087 · protein coding · Open Targets profile
Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Involved in the regulation of endothelial activation, neutrophil adhesion and transendothelial migration (PubMed:36932076). Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. Phosphorylates SCIMP on 'Tyr- 107'; this enhances binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective cytokine response to lipopolysaccharide in macrophages (By similarity). Phosphorylates CLNK (By similarity). Phosphorylates BCAR1/CAS and NEDD9/HEF1 (PubMed:9020138). {ECO:0000250|UniProtKB:P25911, ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:10748115, ECO:0000269|PubMed:10891478, ECO:0000269|PubMed:11435302, ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:11825908, ECO:0000269|PubMed:14726379, ECO:0000269|PubMed:15795233, ECO:0000269|PubMed:16467205, ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:17977829, ECO:0000269|PubMed:18056483, ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18235045, ECO:0000269|PubMed:18577747, ECO:0000269|PubMed:18802065, ECO:0000269|PubMed:19290919, ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:36122175, ECO:0000269|PubMed:36932076, ECO:0000269|PubMed:7687428, ECO:0000269|PubMed:9020138}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- GO CC high conf, UniProt loc med conf, Human Protein Atlas loc
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.18463000655174255 (upper bound 0.2991499900817871). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 18 registry trials, updated in the last three years, of the most advanced drugs against LYN (bosutinib, tolimidone, ilorasertib, bafetinib, ENMD-981693, TG100-801), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Daniel J RenoufBCCA - Vancouver Cancer Centre, Vancouver BC, Canada · 1 of 1 trials Phase 2+
- Elias JabbourM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
- Fernando L PaganGeorgetown Univeristy · 1 of 1 trials Phase 2+
- Haruhisa InoueKyoto University · 1 of 1 trials Phase 2+
- Henrik Hjorth-HansenSt. Olavs Hospital · 1 of 1 trials Phase 2+
- Javier Pinilla-IbarzH. Lee Moffitt Cancer Center and Research Institute · 1 of 1 trials Phase 2+
- Kendra L SweetSWOG Cancer Research Network · 1 of 1 trials Phase 2+
- Lillian SiuUniv. Health Network-OCI/Princess Margaret Hospital, Toronto, ON Canada · 1 of 1 trials Phase 2+
- Lydia RoyCentre Hospitalo-Universitaire Henri Mondor, Service d'Hematologie Clinique · 1 of 1 trials Phase 2+
- Martha P. MimsBaylor College of Medicine · 1 of 1 trials Phase 2+
- Tom Christian MartinsenSt Olavs Hospital, Clinical of Internal Medicine · 1 of 1 trials Phase 2+
- Valentin GarciaHospital Ramon y Cajal · 1 of 1 trials Phase 2+
- Claudine IsaacsGeorgetown University · 0 of 1 trials Phase 2+
Registry trials of bosutinib, tolimidone, ilorasertib, bafetinib, ENMD-981693, TG100-801 updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 11 of 17 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 1 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
14 trials of drugs against LYN were stopped early; 3 give no reason
Terminated, withdrawn and suspended interventional trials of bosutinib, tolimidone, ilorasertib, bafetinib, ENMD-981693, TG100-801, JNJ-26483327, XL-228, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 14 most recent of 14.
- terminated · 2024-03-19 · Fundacion Espanola para la Curacion de la Leucemia Mieloide Cronica · Bosutinib 400 MG Monotherapy, Bosutinib 400 MG + Atezolizumab 840 MG in 14 ML Injection“The study has been prematurely terminated due to the onset of 2 dose limiting toxicities in 2 patients.”
- terminated · 2023-07-17 · M.D. Anderson Cancer Center · Ilorasertib“Study terminated due to company's decision to discontinue drug development”
- terminated · 2022-07-01 · Milton S. Hershey Medical Center · matched by the registry's drug synonyms“Product complaint”
- withdrawn · 2022-06-09 · City of Hope Medical Center · Bosutinib Monohydrate“Drug availability”
- terminated · 2021-12-30 · Pfizer · BosutinibNo reason given
- terminated · 2021-09-27 · Pfizer · Bosutinib“See termination reason in detailed description.”
- terminated · 2020-11-19 · M.D. Anderson Cancer Center · Bosutinib“Terminated per PI's request at the time of CR. Study was closed due to low/slow accrual due to other competing studies.”
- terminated · 2020-05-11 · M.D. Anderson Cancer Center · Bosutinib“Terminated per PI's request due to competing priorities.”
- terminated · 2015-08-21 · Exelixis · matched by the registry's drug synonyms“Sponsor decision”
- terminated · 2015-08-21 · Exelixis · matched by the registry's drug synonyms“Sponsor decision”
- terminated · 2014-05-09 · University of California, San Francisco · Gemcitabine, Bosutinib“Terminated due to slow accrual”
- terminated · 2013-02-22 · Pfizer · BosutinibNo reason given
- terminated · 2012-11-05 · Pfizer · Bosutinib“See termination reason in detailed description.”
- terminated · 2010-03-29 · TargeGen · matched by the registry's drug synonymsNo reason given
Paediatric incentives and obligations for LYN's drugs
For bosutinib, tolimidone, ilorasertib, bafetinib, ENMD-981693, TG100-801, JNJ-26483327, XL-228: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · LYN is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-000727-PIP01-09-M07 (Bosutinib, Treatment of chronic myeloid leukaemia (CML)): PM: decision on the application for modification of an agreed PIP, 7 Aug 2023; compliance positive 15 Dec 2023Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-000727-PIP01-09-M07, 2026-11-11
- EU orphan designation: yes · EU/3/10/762 withdrawn 4 Aug 2010: Treatment of chronic myeloid leukaemia; EU/3/10/731 withdrawn 10 Jun 2010: Treatment of chronic myeloid leukaemiaRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Bosulif: authorised since 27 Mar 2013Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA EPAR Bosulif, 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: yes · Bosutinib [Bosulif], 26 Sept 2023: Treatment of adult and pediatric patients 1 year of age and older with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML), newly-diagnosed or resistant or intolerant to prior therapyRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 3 interventional studies of bosutinib, tolimidone, ilorasertib, bafetinib, enmd-981693, tg100-801, jnj-26483327, xl-228 include patients under 18; 2 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 9 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.